Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cadmium Compounds/pharmacology , Macrophages/drug effects , Naproxen/pharmacology , Quantum Dots , Tellurium/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Cadmium Compounds/chemical synthesis , Humans , Macrophages/cytology , Models, Chemical , Naproxen/chemical synthesisABSTRACT
We describe the synthesis of a series of AMD3100-lipid and AMD3100-polycationic conjugates which were used as components of targeted lipoplexes (in conjunction with (poly)cationic lipids) and polyplexes, respectively, for mediating specific gene transfer into cells expressing CXCR4 which displays a high affinity for AMD3100. Transfection studies were investigated with suspension CXCR4(+) human lymphoma Jurkat cells and with adherent CXCR4(-) human glioblastoma T98G and human lung carcinoma A549 cells lines in order to demonstrate a receptor-mediated endocytosis pathway and to minimize nonspecific transfection pathways. Altogether, our results show that polyplexes formulated with AMD-labeled polymers constitute, under certain conditions, specific gene transfer systems into suspension CXCR4(+) Jurkat cells. This is more particularly the case when the nonspecific transfection pathways are minimized (i.e. for N/P Subject(s)
Gene Targeting/methods
, Heterocyclic Compounds/administration & dosage
, Receptors, Chemokine/biosynthesis
, Receptors, Chemokine/genetics
, Transfection/methods
, Benzylamines
, Cell Line, Tumor
, Cell Survival/drug effects
, Cell Survival/physiology
, Cyclams
, Gene Expression Regulation/drug effects
, Gene Expression Regulation/physiology
, Genetic Therapy/methods
, Heterocyclic Compounds/chemistry
, Humans
, Jurkat Cells
, Receptors, CXCR4
, Receptors, Chemokine/metabolism
ABSTRACT
We report on the synthesis of a series of polycationic telomers, polycationic diblock and random polyethylene glycol (PEG)-grafted (co)telomers, and polycationic random tris(hydroxymethyl)methyl (THM) cotelomers, and on their in vitro gene transfer capability. These compounds were obtained by a telomerization process of various amino-, tetraethylene glycol-, or THM-acrylamide taxogens with thiols which might derive from PEG2000. For N/P ratios [N is the number of (co)telomer amine equivalents; P is the number of DNA phosphate equivalents] from 0.8 to 10, these (co)telomers condensed DNA, forming (co)teloplexes with mean sizes in the 85-330 nm range, even for an N/P ratio of 0.8 or 1.25. Some structure-transfection efficiency relationships were established. Among the new polycationic derivatives that were synthesized and investigated for their transfection efficiency, the (i)Bu-[NH](75) telomers and the diblock polyethylene glycol-conjugated PEG2000-[NH](n) telomers are very promising candidates for gene transfer purposes.
